In vitro chemosensitivity of leukemic progenitor cells (AML-CFU) to a combination of mafosfamide lysine (ASTA-Z 7654) and etoposide (VP16-213).
The inhibitory effects of mafosfamide lysine, ASTA-Z 7654 (ASTA-Z) and etoposide, (VP16-213) on human leukemic progenitor cells (AML-CFU) were studied using a clonogenic assay. AML-CFU were shown to be less sensitive than human promyelocytic leukemia cells (HL-60) to the toxic effects of these two drugs. The mean log kill obtained for the AML-CFU from 12 patients was only 0.95 and 0.93 for 50 micrograms/ml ASTA-Z and etoposide respectively. For normal progenitor cells (CFU-GM) the maximum log kill increased to 2 log at 50 micrograms/ml ASTA-Z or etoposide and for HL-60 cells more than 4 log kill values were obtained for the same drug concentrations. When the two drugs were used in combination the log kill value increased to 1.75 for AML-CFU. Furthermore, in addition to classic incubation parameters (temperature, cell concentration, red blood cell contamination and time) the treatment efficiency was influenced by the incubation sequence of the two drugs. When ASTA-Z and etoposide were incubated together (Z/VP) or etoposide prior to ASTA-Z (VP + Z) log kill values for drug concentrations of 20 and 50 micrograms/ml were 0.72 and 1.41 respectively. However, when cells were incubated with ASTA-Z prior to etoposide (Z + VP) values of 1.1 and 1.75 were obtained for drug concentrations of 20 and 50 micrograms/ml respectively (p less than or equal to 0.05 between Z + VP and the two other sequences).(ABSTRACT TRUNCATED AT 250 WORDS)
Deconinck
E
E
Unité de greffe de moelle osseuse, CHU Jean Minjoz, Besançon, France.
Tamayo
E
E
Hervé
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005047:Etoposide / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D005047:Etoposide; D003520:Cyclophosphamide; C047251:mafosfamide-lysine